1. Field of the Invention
This invention is directed to the synthesis and purification of 3,3-dimethylbutyraldehyde. In particular, the present invention is related to the oxidation of 1-chloro-3,3-dimethylbutane with dimethyl sulfoxide (DMSO) to form 3,3-dimethylbutyraldehyde followed by the purification of the crude product.
2. Related Background Art
1-Chloro-3,3-dimethylbutane can be synthesized by treating tert-butyl chloride and ethylene with aluminum trichloride as reported in Acta Chem. Scand., Vol. 13 (1959), page 612, the disclosure of which is incorporated herein by reference. The oxidation of benzyl halides by dimethyl sulfoxide into benzyl aldehydes was reported in Journal American of Chemical Society, Vol. 81 (1959), pages 4113-4114, and Journal of Organic Chemistry, Vol. 24 (1959), pages 1792-1793. The oxidation of primary halides, which are activated by an adjacent carbonyl group, by dimethyl sulfoxide into the corresponding aldehydes was reported in Journal of American Chemical Society, Vol. 79 (1957), page 6562, and Journal of Organic Chemistry, Vol. 23 (1958), page 1563.
The oxidation of primary aliphatic chlorides and bromides by dimethyl sulfoxide in the presence of 1.5 equivalent NaI was reported in Synthetic Communications, Vol. 16 (1986), pages 1343-1346. The reaction was reported to yield the corresponding aldehydes in 56-96% yield. This article does not disclose the oxidation of 1-chloro-3,3-dimethylbutane and does not suggest that a catalytic amount of iodide is effective for the oxidation. Journal of American Chemical Society, Vol. 81 (1959), page 4113-4114, and Tetrahedron Letter (1974), page 917-920 disclose that simple primary chlorides and bromides can be converted to tosylates or tetrafluoroborates followed by oxidation with dimethyl sulfoxide to generate aldehydes.
U.S. Pat. No. 4,175,204 describes the use of sodium bromide with activated allyl chloride. A substituted allyl chloride was oxidized to its corresponding aldehyde with DMSO in the presence of catalytic amounts of sodium bromide.
3,3-Dimethylbutyraldehyde is an intermediate that is useful in the preparation of the sweetener N-N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl!-L-phenylalanine, 1-methyl ester, disclosed in U.S. Pat. No. 5,480,668 and U.S. Pat. No. 5,510,508. Commercially available 3,3-dimethylbutyraldehyde is currently prepared using methods that are very costly and that result in a product that is not commercially practicable.
Several methods are known for the preparation of 3,3-dimethylbutyraldehyde by the oxidation of 3,3-dimethyl butanol, as described in EP 0391652; EP 0374952; Journal of Organic Chemistry, Vol. 54, p. 570 (1989); Journal of Organic Chemistry, Vol. 61, p. 2918 (1996); and Journal of the American Chemical Society, Vol. 103, p. 4473 (1981). There is no method reported, however, that prepares 3,3-dimethylbutyraldehyde by the oxidation of 1-chloro-3,3-dimethylbutane.
Furthermore, the crude product from the oxidation of 1-chloro-3,3-dimethylbutane with DMSO typically contains dimethyl disulfide and dimethyl sulfide, besides other sulfur and non-sulfur containing impurities. Conventional distillation would not be able to separate dimethyl disulfide (boiling point 109.degree. C.) from 3,3-dimethylbutyraldehyde (boiling point 104-106.degree. C.) because their boiling points are very close. Contamination by even trace amounts of an organic sulfur impurities in 3,3-dimethylbutyraldehyde is highly undesirable for its use in the synthesis of N-N-(3,3- dimethyl)-L-.alpha.-aspartyl!-L-phenylalanine, 1-methyl ester, which is typically produced by the hydrogenation of a mixture of 3,3-dimethylbutyraldehyde and aspartame in the presence of a precious metal catalyst. It is well known that such catalysts can be deactivated by organic sulfur compounds. Thus, any organic sulfur impurity in 3,3-dimethylbutyraldehyde must be removed before its hydrogenation with aspartame. Accordingly, it is highly desired to develop a purification procedure which can remove all impurities, including sulfur-containing compounds, in the crude 3,3-dimethylbutyraldehyde products.
Purification of aldehydes by their conversion into a solid aldehyde/bisulfite adduct has been described in the literature. "Purification of Laboratory Chemicals" (Pergamon Press, 1988) pages 60-61 is incorporated by reference herein as general reference for this methodology.
Chemical Pharmaceutical Bulletin Vol, 26 (1978) pages 3233-3236, incorporated by reference herein, discloses a method of purifying 3,3-dimethylbutyraldehyde, which was synthesized from the reaction of the neo-hexyl magnesium bromide with orthoformate, by its conversion into a 3,3-dimethylbutyraldehyde/sodium bisulfite adduct, followed by aldehyde regeneration with aqueous sodium bicarbonate. This purification involved the following steps: stirring a mixture of the isolated crude product and aqueous sodium bisulfite solution at room temperature overnight; isolating the solid 3,3-dimethylbutyraldehyde/sodium bisulfite adduct by filtration; washing the isolated solid adduct and the aqueous filtrate with ether; combining the washed isolated solid adduct with the aqueous filtrate and sodium bicarbonate to form a mixture; and steam-distilling the mixture. Further manipulation gave the purified 3,3-dimethylbutyraldehyde. However, this procedure was not designed for the removal of trace amounts of organic sulfur compounds from the aldehyde and can not give 3,3-dimethylbutyraldehyde that is free of organic sulfur contamination as required for the synthesis of N-(N(3,3-dimethyl)-L-.alpha.-aspartyl)-L-phenylalanine, 1-methyl ester.
Accordingly, a method for preparing 3,3dimethylbutyraldehyde which is both economical and of greater purity is highly desired.